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Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis.
Burdziak, Cassandra; Alonso-Curbelo, Direna; Walle, Thomas; Reyes, José; Barriga, Francisco M; Haviv, Doron; Xie, Yubin; Zhao, Zhen; Zhao, Chujun Julia; Chen, Hsuan-An; Chaudhary, Ojasvi; Masilionis, Ignas; Choo, Zi-Ning; Gao, Vianne; Luan, Wei; Wuest, Alexandra; Ho, Yu-Jui; Wei, Yuhong; Quail, Daniela F; Koche, Richard; Mazutis, Linas; Chaligné, Ronan; Nawy, Tal; Lowe, Scott W; Pe'er, Dana.
Afiliación
  • Burdziak C; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Alonso-Curbelo D; Tri-Institutional Training Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
  • Walle T; Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Reyes J; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
  • Barriga FM; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Haviv D; Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
  • Xie Y; Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, 69120 Heidelberg, Germany.
  • Zhao Z; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
  • Zhao CJ; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Chen HA; Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Chaudhary O; Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Masilionis I; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Choo ZN; Tri-Institutional Training Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
  • Gao V; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Luan W; Tri-Institutional Training Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
  • Wuest A; Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Ho YJ; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Wei Y; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Quail DF; Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
  • Koche R; Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Mazutis L; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Chaligné R; Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Nawy T; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Lowe SW; Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Pe'er D; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Science ; 380(6645): eadd5327, 2023 05 12.
Article en En | MEDLINE | ID: mdl-37167403
The response to tumor-initiating inflammatory and genetic insults can vary among morphologically indistinguishable cells, suggesting as yet uncharacterized roles for epigenetic plasticity during early neoplasia. To investigate the origins and impact of such plasticity, we performed single-cell analyses on normal, inflamed, premalignant, and malignant tissues in autochthonous models of pancreatic cancer. We reproducibly identified heterogeneous cell states that are primed for diverse, late-emerging neoplastic fates and linked these to chromatin remodeling at cell-cell communication loci. Using an inference approach, we revealed signaling gene modules and tissue-level cross-talk, including a neoplasia-driving feedback loop between discrete epithelial and immune cell populations that was functionally validated in mice. Our results uncover a neoplasia-specific tissue-remodeling program that may be exploited for pancreatic cancer interception.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Páncreas / Neoplasias Pancreáticas / Epigénesis Genética / Carcinogénesis Límite: Animals Idioma: En Revista: Science Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Páncreas / Neoplasias Pancreáticas / Epigénesis Genética / Carcinogénesis Límite: Animals Idioma: En Revista: Science Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos